JP5688233B2 - TARC production inhibitor - Google Patents
TARC production inhibitor Download PDFInfo
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- JP5688233B2 JP5688233B2 JP2010099391A JP2010099391A JP5688233B2 JP 5688233 B2 JP5688233 B2 JP 5688233B2 JP 2010099391 A JP2010099391 A JP 2010099391A JP 2010099391 A JP2010099391 A JP 2010099391A JP 5688233 B2 JP5688233 B2 JP 5688233B2
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- tarc
- tarc production
- production inhibitor
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Description
本発明は、経口投与組成物に関し、さらに詳しくは、次に示す成分の1種又は2種以上から選択されることを特徴とする、TARC(Thymus and activation−regulated chemokine)産生抑制剤に関する。
(成分)エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート、リコカルコンA、ペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニン、ルテオリン、レスベラトロール、リポテイコ酸及び/又はその塩、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸及び/又はその誘導体、アスタキサンチン、β−カロテン、オキシ脂肪酸
The present invention relates to a composition for oral administration, and more particularly, to a TARC (Thymus and activation-regulated chemokine) production inhibitor characterized by being selected from one or more of the following components.
(Component) epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate, lycochalcone A, pedunclazine, rugosin C, casarrictin, isostrichtinin, strictinin, luteolin, Resveratrol, lipoteichoic acid and / or salt thereof, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, L-ascorbic acid and / or a derivative thereof, astaxanthin, β-carotene, oxy fatty acid
TARC(Thymus and activation−regulated chemokine)とは、白血球細胞に特異的に作用するケモカインの1つで71個のアミノ酸より構成されるタンパク質である(例えば、非特許文献1、非特許文献2を参照)。例えばアトピー性皮膚炎のようなアレルギー性疾患の病勢指標の1つとして血中TARC値が用いられているが、その根拠として病変部の表皮角化細胞により過剰に産生されたTARCがリンパ球(ケモカインレセプター4を発現するTh2細胞)を局所的に遊走させ、Th2優位の免疫応答により、IgE産生や好酸球の浸潤・活性化が惹起された結果、アレルギー症状が引き起こされると考えられている(例えば、非特許文献3、非特許文献4を参照)。しかしながら、アレルギー性疾患を有さない健常者において、肌荒れとTARC産生との関連性については全く知られていなかった。 TARC (Thymus and activation-regulated chemokine) is a chemokine that specifically acts on white blood cells and is a protein composed of 71 amino acids (see, for example, Non-Patent Document 1 and Non-Patent Document 2). ). For example, the blood TARC value is used as one of the disease index of allergic diseases such as atopic dermatitis. As a basis for this, TARC excessively produced by epidermis keratinocytes in the lesion is lymphocytes ( It is thought that allergic symptoms are caused as a result of Th2 dominant immune response causing IgE production and eosinophil infiltration / activation by locally migrating (Th2 cells expressing chemokine receptor 4). (For example, refer nonpatent literature 3 and nonpatent literature 4.). However, the relationship between rough skin and TARC production has not been known at all in healthy individuals who do not have allergic diseases.
一方、TARCの産生を抑制することによってこの様なアレルギー症状を抑えることが考えられ、その様な効果を有する成分としては、タンニン酸、ケルセチン(例えば、非特許文献5を参照)や、オロパタジン(例えば、非特許文献6を参照)などが知られているが、アレルギー性疾患を有さない、健常者の肌荒れを改善することができる、TARC産生抑制剤については全く知られていなかった。 On the other hand, it is conceivable to suppress such allergic symptoms by suppressing the production of TARC. Examples of components having such an effect include tannic acid, quercetin (see, for example, Non-Patent Document 5), olopatadine ( For example, see Non-Patent Document 6), but no TARC production inhibitor capable of improving rough skin of healthy subjects who do not have allergic diseases has been known.
逆に、エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート等のカテキン類や(例えば、特許文献1、特許文献2、特許文献3、特許文献4、特許文献5を参照)、リコカルコンA等の甘草抽出成分(例えば、特許文献6、特許文献7、特許文献8、特許文献9、特許文献10を参照)については、抗アレルギー作用や抗炎症作用が広く知られているが、このような成分がアレルギー性疾患を有さない、健常者の肌荒れを改善することができる、TARC産生抑制作用を有するということもこれまで全く知られていなかった。 Conversely, catechins such as epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate and the like (for example, Patent Document 1, Patent Document 2, Patent Document) 3, see Patent Literature 4 and Patent Literature 5), and licorice extract components such as licochalcone A (for example, see Patent Literature 6, Patent Literature 7, Patent Literature 8, Patent Literature 9, and Patent Literature 10). Although it has been widely known for its action and anti-inflammatory action, it has never been known that such a component has a TARC production inhibitory action that does not have allergic diseases and can improve rough skin of healthy subjects. It was not done.
その他ペドゥンクラジン、カスアリクチン、ルゴシンC、ストリクチニン等のクルミポリフェノール、ルテオリン、レスベラトロール、リポテイコ酸及び/又はその塩、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸及び/又はその誘導体、アスタキサンチン、β−カロテン、オキシ脂肪酸といった既知の成分についても、アレルギー性疾患を有さない、健常者の肌荒れを改善することができる、TARC産生抑制作用を有するということはこれまで全く知られていなかった。 Others such as pedunclazine, casarrictin, rugosin C, strictinin, walnut polyphenols, luteolin, resveratrol, lipoteichoic acid and / or salts thereof, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, L-ascorbic acid and / or The known ingredients such as derivatives, astaxanthin, β-carotene, and oxyfatty acid have been known so far to have a TARC production inhibitory action that can improve the rough skin of healthy people who do not have allergic diseases. It was not done.
本発明は、この様な状況下為されたものであり、アレルギー性疾患を有さない、健常者の肌荒れを改善することができる、TARC産生抑制剤を提供することを課題とする。 The present invention has been made under such circumstances, and an object of the present invention is to provide a TARC production inhibitor that can improve rough skin of a healthy person who does not have an allergic disease.
この様な状況に鑑みて、本発明者らはアレルギー性疾患を有さない健常者の肌荒れを改善することができる、TARC産生抑制作用を有する物質を求めて、鋭意研究努力を重ねた結果、エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート、リコカルコンA、ペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニン、ルテオリン、レスベラトロール、リポテイコ酸及び/又はその塩、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸及び/又はその誘導体、アスタキサンチン、β−カロテン、オキシ脂肪酸から選択される成分にその様な作用を見出し、本発明を完成させるに至った。即ち、本発明は以下に示すとおりである。
(1)次に示す成分の1種又は2種以上から選択されることを特徴とする、TARC産生抑制剤。
(成分)エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート、リコカルコンA、ペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニン、ルテオリン、レスベラトロール、リポテイコ酸及び/又はその塩、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸及び/又はその誘導体、アスタキサンチン、β−カロテン、オキシ脂肪酸
(2)(1)に記載のオキシ脂肪酸が、9−ヒドロキシ−10(E),12(Z)−オクタデカジエン酸、13−ヒドロキシ−9(E),11(E)−オクタデカジエン酸、9−ヒドロキシ−10(E),12(E)−オクタデカジエン酸の1種又は2種以上から選択されることを特徴とする、(1)に記載のTARC産生抑制剤。
(3)(1)又は(2)何れかに記載のTARC産生抑制剤を含有することを特徴とする、経口投与組成物。
(4)食品であることを特徴とする、(3)に記載の経口投与組成物。
(5)アレルギー性疾患を有さない、健常者に対する肌荒れ改善用であることを特徴とする、(1)又は(2)何れかに記載のTARC産生抑制剤。
In view of such a situation, the present inventors sought for a substance having a TARC production inhibitory action, which can improve rough skin of a healthy person who does not have an allergic disease. Epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate, lycochalcone A, pedunclazine, rugosin C, casarrictin, isostrictinin, strictinin, luteolin, resveratrol , Lipoteichoic acid and / or salt thereof, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, L-ascorbic acid and / or a derivative thereof, astaxanthin, β-carotene, oxy fatty acid, and so on To find the effective action and to complete the present invention. It was. That is, the present invention is as follows.
(1) A TARC production inhibitor characterized by being selected from one or more of the following components.
(Component) epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate, lycochalcone A, pedunclazine, rugosin C, casarrictin, isostrichtinin, strictinin, luteolin, Resveratrol, lipoteichoic acid and / or salt thereof, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, L-ascorbic acid and / or a derivative thereof, astaxanthin, β-carotene, oxy fatty acid (2) (1) ) Is a 9-hydroxy-10 (E), 12 (Z) -octadecadienoic acid, 13-hydroxy-9 (E), 11 (E) -octadecadienoic acid, 9-hydroxy- One of 10 (E) and 12 (E) -octadecadienoic acid Characterized in that it is selected from 2 or more, TARC production inhibitor according to (1).
(3) An orally administered composition comprising the TARC production inhibitor according to (1) or (2).
(4) The composition for oral administration according to (3), which is a food.
(5) The TARC production inhibitor according to any one of (1) and (2), which is used for improving rough skin on healthy subjects who do not have an allergic disease.
本発明によれば、優れたTARC産生抑制剤を提供することができる。 According to the present invention, an excellent TARC production inhibitor can be provided.
本発明のTARC産生抑制剤は、エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート、リコカルコンA、ペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニン、ルテオリン、レスベラトロール、リポテイコ酸及び/又はその塩、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸及び/又はその誘導体、アスタキサンチン、β−カロテン、オキシ脂肪酸から選択される、1種又は2種以上を必須成分として含有することを特徴とする。これらの中で、エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレートは市販の精製品を使用しても良いが、かかる成分は茶葉に多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良い。前記茶葉を基源とする茶としては、べにふうきと呼ばれるアッサム種の品種のものが好ましく例示でき、例えば、アサヒ飲料株式会社から市販されている、「リョクチャエキスパウダー18334」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 The TARC production inhibitor of the present invention includes epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate, lycochalcone A, pedunclazine, rugocin C, casarrictin, iso Strictinin, strictinin, luteolin, resveratrol, lipoteichoic acid and / or salt thereof, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, L-ascorbic acid and / or derivatives thereof, astaxanthin, β-carotene, oxy 1 type or 2 types or more selected from a fatty acid are contained as an essential component, It is characterized by the above-mentioned. Among these, epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate may be a commercially available purified product. It is known that it is contained in a large amount in tea leaves, and such a component extracted from such a plant body according to a conventional method may be used as a TARC production inhibitor. The tea based on the tea leaves is preferably exemplified by an Assam variety called Benifuuki. For example, “Ryokucha Extract Powder 18334” commercially available from Asahi Beverage Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるリコカルコンAは市販の精製品を使用しても良いが、かかる成分はマメ科甘草に多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、丸善製薬株式会社から市販されている、「リコゲン」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 Lycochalcone A, which is a component of the TARC production inhibitor of the present invention, may be a commercially available refined product, but such a component is known to be contained in a large amount in legume licorice, and such plants A TARC production inhibitor obtained by extracting such components from the body according to a conventional method may be used. For example, “Lycogen” commercially available from Maruzen Pharmaceutical Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニンはクルミ科クルミに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、オリザ油株式会社から市販されている、「クルミ種子ポリフェノール」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 It is known that pedunclazine, rugosin C, casarrictin, isostriktinin, and strictinin, which are constituent components of the TARC production inhibitor of the present invention, are contained in a large amount in the walnut family walnut. May be used as a TARC production inhibitor. For example, “walnut seed polyphenol” commercially available from Oriza Oil Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるルテオリンは市販の精製品を使用しても良いが、かかる成分はシソ科ローズマリー、シソ科シソ、シソ科エゴマに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、日本粉末薬品株式会社から市販されている、「シソ抽出物」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.2質量%〜10質量%含有することが好ましく、2質量%〜5質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、2質量%〜30質量%含有することが好ましく、20質量%〜25質量%含有することがさらに好ましい。 Luteolin, which is a component of the TARC production inhibitor of the present invention, may be a commercially available refined product, but it is known that such components are contained in a large amount in Lamiaceae rosemary, Lamiaceae perilla and Lamiaceae egoma. What is extracted from such a plant body according to a conventional method may be used as a TARC production inhibitor, for example, “Perilla extract” commercially available from Nippon Powder Chemical Co., Ltd. may be used. . In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.2% by mass to 10% by mass, and more preferably 2% by mass to 5% by mass. Moreover, when using a commercially available extract, it is preferable to contain 2 mass%-30 mass% of extract in a total amount, and it is more preferable to contain 20 mass%-25 mass%.
本発明のTARC産生抑制剤の構成成分であるレスベラトロールは市販の精製品を使用しても良いが、かかる成分はブドウ科ブドウに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、サンブライト株式会社から市販されている、「VINEATROL(登録商標)20M」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.2質量%〜10質量%含有することが好ましく、2質量%〜5質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、2質量%〜30質量%含有することが好ましく、20質量%〜25質量%含有することがさらに好ましい。 Resveratrol, which is a component of the TARC production inhibitor of the present invention, may use a commercially available refined product, but it is known that such a component is contained in a large amount in grape vines. What extracted this component from the plant body according to the usual method is good also as a TARC production inhibitor, For example, you may use "VINEATROL (trademark) 20M" marketed from Sun Bright Corporation. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.2% by mass to 10% by mass, and more preferably 2% by mass to 5% by mass. Moreover, when using a commercially available extract, it is preferable to contain 2 mass%-30 mass% of extract in a total amount, and it is more preferable to contain 20 mass%-25 mass%.
本発明のTARC産生抑制剤の構成成分であるリポテイコ酸及び/又はその塩はかかる成分の1種又は2種以上から選択されることが好ましいが、リポテイコ酸が特に好ましく例示される。かかる成分は乳酸菌等のグラム陽性菌の細胞膜に多く含まれていることが知られており、この様な菌体を無加工のまま用いTARC産生抑制剤としても良く、例えば、亀田製菓株式会社から市販されている、「植物性乳酸菌K2」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.01質量%〜1質量%含有することが好ましく、0.1質量%〜0.5質量%含有することがさらに好ましい。また、菌体そのものを用いる場合、菌体そのものを、0.5質量%〜10質量%含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 The lipoteichoic acid and / or salt thereof, which is a component of the TARC production inhibitor of the present invention, is preferably selected from one or more of these components, and lipoteichoic acid is particularly preferred. Such a component is known to be contained in a large amount in the cell membrane of gram-positive bacteria such as lactic acid bacteria. Such cells can be used unprocessed as a TARC production inhibitor, for example, from Kameda Seika Co., Ltd. Commercially available “plant lactic acid bacteria K2” may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.01% by mass to 1% by mass, and more preferably 0.1% by mass to 0.5% by mass. Moreover, when using the microbial cell itself, the microbial cell itself is preferably contained in an amount of 0.5 mass% to 10 mass%, more preferably 1 mass% to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるクルクミンは市販の精製品を使用しても良いが、かかる成分はショウガ科ウコンに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、株式会社サビンサジャパンコーポレーションから市販されている、「クルクミノイド90%FJ」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 Curcumin, which is a component of the TARC production inhibitor of the present invention, may be a commercially available purified product, but it is known that such a component is contained in a large amount in ginger family turmeric. The component extracted from the above according to a conventional method may be used as a TARC production inhibitor, for example, “curcuminoid 90% FJ” commercially available from Sabinsa Japan Corporation may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるオイゲノールは市販の精製品を使用しても良いが、かかる成分はフトモモ科チョウジノキに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、日本粉末薬品株式会社から市販されている、「チョウジ粉末」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.2質量%〜10質量%含有することが好ましく、2質量%〜5質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、2質量%〜30質量%含有することが好ましく、20質量%〜25質量%含有することがさらに好ましい。 Eugenol, which is a constituent component of the TARC production inhibitor of the present invention, may be a commercially available refined product, but it is known that such a component is contained in a large amount in the myrtaceae, such a plant body. Therefore, the TARC production inhibitor may be obtained by extracting the components from the above according to a conventional method. For example, “Choji powder” commercially available from Nippon Powder Chemical Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.2% by mass to 10% by mass, and more preferably 2% by mass to 5% by mass. Moreover, when using a commercially available extract, it is preferable to contain 2 mass%-30 mass% of extract in a total amount, and it is more preferable to contain 20 mass%-25 mass%.
本発明のTARC産生抑制剤の構成成分であるナリンギンは市販の精製品を使用しても良いが、かかる成分はミカン科グレープフルーツやミカン科ハッサクに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、ハリマ漢方製薬から市販されている、「青ハッサクエキス」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.2質量%〜10質量%含有することが好ましく、2質量%〜5質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、2質量%〜30質量%含有することが好ましく、20質量%〜25質量%含有することがさらに好ましい。 Naringin, which is a component of the TARC production inhibitor of the present invention, may use a commercially available refined product, but it is known that such a component is contained in a large amount in Citrus grapefruit and Citrus Hassaku. A TARC production inhibitor obtained by extracting such a component from such a plant according to a conventional method may be used, for example, “Blue Hassaku Extract” commercially available from Harima Kampo Pharmaceutical. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.2% by mass to 10% by mass, and more preferably 2% by mass to 5% by mass. Moreover, when using a commercially available extract, it is preferable to contain 2 mass%-30 mass% of extract in a total amount, and it is more preferable to contain 20 mass%-25 mass%.
本発明のTARC産生抑制剤の構成成分である6−ショウガオールは市販の精製品を使用しても良いが、かかる成分はショウガ科ショウガに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、サビンサジャパンコーポレーションから市販されている、「ジンジャーソフト抽出物20%」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 Although 6-shogaol, which is a constituent component of the TARC production inhibitor of the present invention, may use a commercially available purified product, it is known that such a component is contained in a large amount in ginger family ginger. A TARC production inhibitor obtained by extracting such a component from a simple plant according to a conventional method may be used, for example, “Ginger Soft Extract 20%” commercially available from Sabinsa Japan Corporation may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるルテオリンは市販の精製品を使用しても良いが、かかる成分はシソ科ローズマリー、シソ科シソ、シソ科エゴマに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、日本粉末薬品株式会社から市販されている、「シソ抽出物」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.2質量%〜10質量%含有することが好ましく、2質量%〜5質量%含有することがさらに好ましい。 Luteolin, which is a component of the TARC production inhibitor of the present invention, may be a commercially available refined product, but it is known that such components are contained in a large amount in Lamiaceae rosemary, Lamiaceae perilla and Lamiaceae egoma. What is extracted from such a plant body according to a conventional method may be used as a TARC production inhibitor, for example, “Perilla extract” commercially available from Nippon Powder Chemical Co., Ltd. may be used. . In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.2% by mass to 10% by mass, and more preferably 2% by mass to 5% by mass.
本発明のTARC産生抑制剤の構成成分であるL−アスコルビン酸及び/又はその誘導体は、かかる成分の1種又は2種以上から選択されることが好ましいが、L−アスコルビン酸が特に好ましく例示される。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.1質量%〜50質量%含有することが好ましく、1〜10質量%含有することがさらに好ましい。 The L-ascorbic acid and / or derivative thereof, which is a constituent component of the TARC production inhibitor of the present invention, is preferably selected from one or more of these components, and L-ascorbic acid is particularly preferably exemplified. The In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.1% by mass to 50% by mass, and more preferably 1-10% by mass.
本発明のTARC産生抑制剤の構成成分であるアスタキサンチンは市販の精製品を使用しても良いが、かかる成分は鮭、イクラ、エビ、カニ、オキアミ等の魚介類、或いはヘマトコッカス藻に多く含まれていることが知られており、この様な生物からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、富士化学工業から市販されている、「富士化学アスタリール(登録商標)」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 Astaxanthin, which is a component of the TARC production inhibitor of the present invention, may use commercially available purified products, but such components are often contained in seafood such as salmon, salmon roe, shrimp, crab, krill, or hematococcus algae. It is known that such a component extracted from such an organism according to a conventional method may be used as a TARC production inhibitor. For example, “Fuji Chemical Asterel (registered ), commercially available from Fuji Chemical Industries, Ltd. Trademark) ”may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるβ−カロテンは市販の精製品を使用しても良いが、かかる成分はデュナリエラに多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、協和発酵バイオ株式会社から市販されている、「バイオカロテン30MCT」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 Β-carotene, which is a component of the TARC production inhibitor of the present invention, may be a commercially available refined product, but such a component is known to be contained in a large amount in Dunaliella. Therefore, the TARC production inhibitor may be obtained by extracting the above components from a conventional method, for example, “Bio-Carotene 30MCT” commercially available from Kyowa Hakko Bio Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤の構成成分であるオキシ脂肪酸は、さらに9−ヒドロキシ−10(E),12(Z)−オクタデカジエン酸、13−ヒドロキシ−9(E),11(E)−オクタデカジエン酸、9−ヒドロキシ−10(E),12(E)−オクタデカジエン酸の1種又は2種以上から選択されることが好ましい。かかる成分の精製品を使用しても良いが、かかる成分はイネ科ハトムギおよびトウガラシ、もぐさ、センブリ、米ふすま等に多く含まれていることが知られており、この様な植物体からかかる成分を定法に従って抽出したものをTARC産生抑制剤としても良く、例えば、株式会社Jハーブから市販されている、「ハトムギエキス粉末」を用いても良い。TARC産生抑制効果を有するためにはかかる成分を、総量で、0.001質量%〜1質量%含有することが好ましく、0.01〜0.1質量%含有することがさらに好ましい。また、市販の抽出物を用いる場合、抽出物を、総量で、0.1質量%〜10質量含有することが好ましく、1質量%〜5質量%含有することがさらに好ましい。 The oxy fatty acid which is a component of the TARC production inhibitor of the present invention is further 9-hydroxy-10 (E), 12 (Z) -octadecadienoic acid, 13-hydroxy-9 (E), 11 (E)-. It is preferably selected from one or more of octadecadienoic acid and 9-hydroxy-10 (E), 12 (E) -octadecadienoic acid. A refined product of such an ingredient may be used. However, such an ingredient is known to be contained in a large amount in gramineous barley and pepper, mogusa, assembly, rice bran and the like. May be used as a TARC production inhibitor, and for example, “barley extract powder” commercially available from J Herb Co., Ltd. may be used. In order to have a TARC production inhibitory effect, the total amount of such components is preferably 0.001 to 1% by mass, and more preferably 0.01 to 0.1% by mass. Moreover, when using a commercially available extract, it is preferable to contain 0.1 to 10 mass% of extract in a total amount, and it is more preferable to contain 1 to 5 mass%.
本発明のTARC産生抑制剤は、生体内において血中TARC値を低下せしめる目的で、経口投与組成物として投与することが好ましい。経口投与組成物としては、例えば、顆粒剤、粉末剤、カプセル剤や、錠剤の形態をとる、経口投与医薬品等が例示でき、それぞれの製剤で許容される任意成分を含有することができる。この様な任意成分としては、塩、砂糖、グルタミン酸ナトリウム、イノシン酸ナトリウム、着色成分、増粘剤、乳化・分散剤、保存料、安定剤、結晶セルロース、乳糖等の賦形剤、アラビヤガムやヒドロキシプロピルセルロース等の結合剤、クロスカルメロースナトリウム、デンプン等の崩壊剤、ステアリン酸マグネシウム等の滑沢剤、矯味、矯臭剤、着色剤、各種ビタミン類等が好ましく例示できる。これらを常法に従って処理することにより、本発明の経口投与組成物を製造することができる。斯くして得られた、本発明の経口投与組成物は、それを飲用することにより、血中TARC値の抑制作用に優れた効果を有する。この様な作用を発揮させるためには、前記植物の抽出物を総量で、1日あたり10〜100000mg、あるいは前記各成分を総量で、1日あたり1〜500mgを1回又は数回に分けて飲用することが好ましい。 The TARC production inhibitor of the present invention is preferably administered as an orally administered composition for the purpose of lowering the blood TARC value in vivo. The oral composition, For example, granule, powders, or capsules, in the form of a tablet, can be exemplified oral medicines etc., it can contain any ingredients that are allowed in each of the preparations . Examples of such optional ingredients, salt, sugar, monosodium glutamate, inosinate sodium, wearing IroNaru minute, increasing Nebazai, emulsifying and dispersing agents, preservatives, stabilizers, crystal cellulose, excipients such as lactose Preferred examples include binders such as arabic gum and hydroxypropyl cellulose, disintegrants such as croscarmellose sodium and starch, lubricants such as magnesium stearate, flavoring agents, flavoring agents, coloring agents, various vitamins and the like. By treating these according to a conventional method, the composition for oral administration of the present invention can be produced. The oral administration composition of the present invention thus obtained has an excellent effect of suppressing the blood TARC value by drinking it. In order to exert such effects, the plant extract is divided into 10 to 100000 mg per day, or 1 to 500 mg per day as a total amount, or once or several times per day. It is preferable to drink.
以下に、実施例を挙げて、本発明について更に詳細に説明を加えるが、本発明が、かかる実施例にのみ限定されないことは言うまでもない。 Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.
<実施例1>TARC産生抑制試験
ヒト皮膚由来表皮細胞株HaCaT cellを用いてTARC産生量の測定を実施した。10容量%牛胎児血清(GIBCO社製)を含むDMEM培地(GIBCO社製)に細胞を懸濁し、6ウェル培養プレートに0.5×10 6 の細胞数を播種し、CO 2 インキュベーター(95容量%空気、5容量%二酸化炭素)内、37℃の条件下で48時間培養した。その後、インターフェロン−γを終濃度10ng/ml、TNF−αを終濃度10ng/ml含有し、牛胎児血清を含まないDMEM培地に交換し、同時にジメチルスルホキ
シドにて懸濁した各成分を終濃度が0.5〜10μMとなるように添加し、さらに24時間培養した。培養上清を回収し、Quantakine Human TARC(R&D
systems社製)を用いてTARCを定量した(n=6)。結果は培地のみをコントロールとしたときの、コントロールに対する比で表した。
<Example 1> TARC production suppression test TARC production was measured using a human skin-derived epidermal cell line HaCaT cell. The cells are suspended in DMEM medium (GIBCO) containing 10% by volume fetal calf serum (GIBCO), seeded with 0.5 × 10 6 cells in a 6-well culture plate, and CO 2 incubator (95 volumes). % Air, 5 vol% carbon dioxide) and cultured at 37 ° C. for 48 hours. Thereafter, the interferon-γ was replaced with a DMEM medium containing 10 ng / ml final concentration of TNF-α and 10 ng / ml TNF-α and not containing fetal calf serum. It added so that it might become 0.5-10 micromol, and also culture | cultivated for 24 hours. The culture supernatant was collected and Quantakine Human TARC (R & D
TARC was quantified using a system) (n = 6). The results were expressed as a ratio to the control when only the medium was used as a control.
図1に結果を示す。これより、エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート、リコカルコンA、ペドゥンクラジン、ルゴシンC、カスアリクチン、イソストリクチニン、ストリクチニン、ルテオリン、レスベラトロール、リポテイコ酸、クルクミン、オイゲノール、ナリンギン、6−ショウガオール、L−カルニチン、L−アスコルビン酸ナトリウム、アスタキサンチン、β−カロテン、9−ヒドロキシ−10(E),12(Z)−オクタデカジエン酸、13−ヒドロキシ−9(E),11(E)−オクタデカジエン酸、9−ヒドロキシ−10(E),12(E)−オクタデカジエン酸は優れたTARC産生抑制作用を有することが判る。 The results are shown in FIG. From this, epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin-3-O- (3-O-methyl) gallate, lycochalcone A, pedunclazine, rugosin C, casarrictin, isostrictinin, strictinin, luteolin, Resveratrol, lipoteichoic acid, curcumin, eugenol, naringin, 6-shogaol, L-carnitine, sodium L-ascorbate, astaxanthin, β-carotene, 9-hydroxy-10 (E), 12 (Z) -octadeca Dienoic acid, 13-hydroxy-9 (E), 11 (E) -octadecadienoic acid, 9-hydroxy-10 (E), 12 (E) -octadecadienoic acid has excellent TARC production inhibitory action I understand.
<実施例2〜25>
以下の表2に示す処方に従って、実施例2〜25として、本願発明の経口投与組成物を作製した。即ち、処方成分を10質量部の水と共に転動相造粒(不二パウダル株式会社製「ニューマルメライザー」)し、打錠して錠剤状の経口投与組成物を得た。本願発明の経口投与組成物は、血中TARC値の抑制作用に優れた効果を示していた。
<Examples 2 to 25>
According to the formulation shown in Table 2 below, oral administration compositions of the present invention were prepared as Examples 2 to 25. That is, the formulation components rolling phase granulated with 10 parts by weight of water (manufactured by Fuji Paudal Co., Ltd., "New Marumerizer") to obtain a tablet-like oral composition is tableted. The composition for oral administration of the present invention showed an excellent effect in suppressing blood TARC value.
<実施例26〜49>
以下の表5に示す処方に従って、実施例26〜49として、本願発明のドリンク製剤の経口投与組成物を作製した。即ち、処方成分を撹拌可溶化しドリンク製剤の経口投与組成物を得た。本願発明の経口投与組成物は、血中TARC値の抑制作用に優れた効果を示していた。
<Examples 26 to 49>
According to the formulation shown in Table 5 below, compositions for oral administration of the drink preparation of the present invention were prepared as Examples 26 to 49. That is, the prescription ingredients were solubilized with stirring to obtain a composition for oral administration of a drink preparation. The composition for oral administration of the present invention showed an excellent effect in suppressing blood TARC value.
Claims (1)
(成分)エピカテキンガレート、エピガロカテキン、エピガロカテキンガレート、エピガロカテキン−3−O−(3−O−メチル)ガレート A TARC production inhibitor , which is for healthy individuals who do not have an allergic disease , comprising a component selected from one or more of the following components .
(Component) epicatechin gallate, epigallocatechin, epigallocatechin gallate, epigallocatechin -3-O- (3-O- methyl) gallate bets
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